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DPP-4 is expressed ...
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Bugliani, MarcoUniversity of Pisa
(author)
DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes
- Article/chapterEnglish2018
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LIBRIS-ID:oai:lup.lub.lu.se:29f386d9-ebb9-46e6-9870-57ecf5aa8998
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https://lup.lub.lu.se/record/29f386d9-ebb9-46e6-9870-57ecf5aa8998URI
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https://doi.org/10.1016/j.mce.2018.01.019DOI
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Language:English
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Summary in:English
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It has been reported that the incretin system, including regulated GLP-1 secretion and locally expressed DPP-4, is present in pancreatic islets. In this study we comprehensively evaluated the expression and role of DPP-4 in islet alpha and beta cells from non-diabetic (ND) and type 2 diabetic (T2D) individuals, including the effects of its inhibition on beta cell function and survival. Isolated islets were prepared from 25 ND and 18 T2D organ donors; studies were also performed with the human insulin-producing EndoC-βH1 cells. Morphological (including confocal microscopy), ultrastructural (electron microscopy, EM), functional (glucose-stimulated insulin secretion), survival (EM and nuclear dyes) and molecular (RNAseq, qPCR and western blot) studies were performed under several different experimental conditions. DPP-4 co-localized with glucagon and was also expressed in human islet insulin-containing cells. Furthermore, DPP-4 was expressed in EndoC-βH1 cells. The proportions of DPP-4 positive alpha and beta cells and DPP-4 gene expression were significantly lower in T2D islets. A DPP-4 inhibitor protected ND human beta cells and EndoC-βH1 cells against cytokine-induced toxicity, which was at least in part independent from GLP1 and associated with reduced NFKB1 expression. Finally, DPP-4 inhibition augmented glucose-stimulated insulin secretion, reduced apoptosis and improved ultrastructure in T2D beta cells. These results demonstrate the presence of DPP-4 in human islet alpha and beta cells, with reduced expression in T2D islets, and show that DPP-4 inhibition has beneficial effects on human ND and T2D beta cells. This suggests that DPP-4, besides playing a role in incretin effects, directly affects beta cell function and survival.
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Syed, FarooqUniversity of Pisa
(author)
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Paula, Flavia M.M.Université Libre de Bruxelles (ULB)
(author)
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Omar, Bilal A.Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-bor
(author)
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Suleiman, MaraUniversity of Pisa
(author)
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Mossuto, SandraUniversity of Pisa
(author)
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Grano, FrancescaUniversity of Pisa
(author)
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Cardarelli, FrancescoScuola Normale Superiore di Pisa
(author)
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Boggi, UgoUniversity of Pisa
(author)
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Vistoli, FabioUniversity of Pisa
(author)
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Filipponi, FrancoUniversity of Pisa
(author)
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De Simone, PaoloUniversity of Pisa
(author)
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Marselli, LorellaUniversity of Pisa
(author)
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De Tata, VincenzoUniversity of Pisa
(author)
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Ahren, BoLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-bah
(author)
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Eizirik, Decio L.Université Libre de Bruxelles (ULB)
(author)
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Marchetti, PieroUniversity of Pisa
(author)
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University of PisaUniversité Libre de Bruxelles (ULB)
(creator_code:org_t)
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In:Molecular and Cellular Endocrinology: Elsevier BV473, s. 186-1930303-7207
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Bugliani, Marco
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Syed, Farooq
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Paula, Flavia M. ...
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Omar, Bilal A.
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Suleiman, Mara
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Mossuto, Sandra
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Grano, Francesca
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Cardarelli, Fran ...
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Boggi, Ugo
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Vistoli, Fabio
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Filipponi, Franc ...
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De Simone, Paolo
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Marselli, Lorell ...
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De Tata, Vincenz ...
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Ahren, Bo
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Eizirik, Decio L ...
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Marchetti, Piero
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